The present invention relates generally to the field of scanners for imaging and evaluating biological microarrays. More particularly, the invention relates to a technique for rapidly and accurately evaluating microarrays through the use of confocal line scanning.
An increasing number of applications are being developed for biological microarrays. Such microarrays typically include Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) probes that are specific for nucleotide sequences present in genes in humans and other organisms. Individual DNA or RNA probes can be attached at specific locations in a small geometric grid on a microarray support. A test sample, such as from a known person or organism, can be exposed to the grid, such that complimentary genes or fragments hybridize to probes at the individual sites in the array. The array can then be examined by scanning specific frequencies of light over the sites to identify which genes or fragments in the sample were present, by fluorescence of the sites at which genes or fragments hybridized.
Such microarrays, sometimes referred to as gene or genome chips, DNA chips, gene arrays, and so forth, may be used for expression profiling, monitoring expression levels, genotyping, sequencing, and so forth. For example, diagnostic uses may include evaluation of a particular patient's genetic makeup to determine whether a disease state is present or whether pre-disposition for a particular condition exists. The reading and evaluation of microarrays is a key to their utility. For example, in certain types of microarrays, DNA probes are attached to beads at individual sites in the array. Because the fragments are attached in a random or statistically varying pattern, it is necessary to image the microarray to determine the location of each of the individual fragments, and their makeup. Moreover, once a sample has been exposed to the microarray, reading the microarray is necessary to determine the makeup of the sample.
Various types of microarray readers have been proposed and are currently in use. In many such readers, a small point of light is scanned across lines of the microarray to cause fluorescence of the individual sites, particularly those sites which genes or fragments are hybridized. Such scanning is preferably extremely fast and accurate. Current microarray designs provide for many thousands of individual sites in a very small area of the substrate. The number of sites and the density of such sites in the array are constantly increasing, posing challenges to known scanning and imaging techniques.
There is a constant need, therefore, for improved microarray scanning and imaging technologies. There is a particular need for a technique that will allow for very fast scanning of a large number of individual sites, and that reduces the potential for errors in imaging.